Development of an Innovative Real-World Evidence Registry for the Herpes Simplex Virus: Case Study - JMIR Dermatology
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JMIR DERMATOLOGY van Velthoven et al
Original Paper
Development of an Innovative Real-World Evidence Registry for
the Herpes Simplex Virus: Case Study
Michelle Helena van Velthoven1, BSc, MSc, PhD; Ching Lam1, MEng; Caroline de Cock1, BSc; Terese Stenfors2,
BSc, MSc, PhD; Hassan Chaudhury3, BSc; Edward Meinert1,3, MA, MSc, MBA, MPA, PhD
1
Digitally Enabled Preventative Health Research Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom
2
Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
3
Department of Primary Care and Public Health, Imperial College London, London, United Kingdom
Corresponding Author:
Edward Meinert, MA, MSc, MBA, MPA, PhD
Digitally Enabled Preventative Health Research Group
Department of Paediatrics
University of Oxford
Headley Way, Headington
John Radcliffe Hospital
Oxford, OX3 9DU
United Kingdom
Phone: 44 7824446808
Email: e.meinert14@imperial.ac.uk
Abstract
Background: Infection with the herpes simplex virus (HSV) is common but not well understood. Furthermore, there remains
a social stigma surrounding HSV that can have psychosocial implications for those infected. Despite many patients infected with
HSV experiencing mild-to-severe physical symptoms, only one subeffective treatment is available. A registry collecting real-world
data reported by individuals potentially infected with HSV could help patients to better understand and manage their condition.
Objective: This study aimed to report on the development of a registry to collect real-world data reported by people who might
be infected with HSV.
Methods: A case study design was selected as it provides a systematic and in-depth approach to investigating the planning
phase of the registry. The case study followed seven stages: plan, design, prepare, collect, analyze, create, and share. We carried
out semistructured interviews with experts, which were thematically analyzed and used to build use cases for the proposed registry.
These use cases will be used to generate detailed models of how a real-world evidence registry might be perceived and used by
different users.
Results: The following key themes were identified in the interviews: (1) stigma and anonymity, (2) selection bias, (3)
understanding treatment and outcome gaps, (4) lifestyle factors, (5) individualized versus population-level data, and (6) severe
complications of HSV. We developed use cases for different types of users of the registry, including individuals with HSV,
members of the public, researchers, and clinicians.
Conclusions: This case study revealed key considerations and insights for the development of an appropriate registry to collect
real-world data reported by people who might be infected with HSV. Further development and testing of the registry with different
users is required. The registry must also be evaluated for the feasibility and effectiveness of collecting data to support symptom
management. This registry has the potential to contribute to the development of vaccines and treatments and provide insights into
the impact of HSV on other conditions.
(JMIR Dermatol 2020;3(1):e16933) doi: 10.2196/16933
KEYWORDS
case study; herpes simplex; herpes simplex virus vaccines; real-world evidence; patient registry
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registry. In addition, clinicians may be unable or unwilling to
Introduction contribute to registries because of time or technical constraints
Background [17]. In recent decades, there has been an increasing focus on
incorporating patient-reported outcomes and real-world data
Globally in 2012, an estimated 3.7 billion people younger than into clinical registries to overcome these issues [11]. Real-world
50 years were infected with herpes simplex virus (HSV) type evidence (RWE) is a subset of evidence-based medicine that
1 (HSV1) and 417 million with HSV type 2 (HSV2) [1]. HSV refers to health care information gathered through means outside
can be contracted through oral or genital contact and is of typical clinical research settings. The increasing ubiquity of
associated with symptoms of varying severity in assorted body the internet has made it more convenient for internet-literate
parts, for example, painful sores on the face (cold sores), genitals patients to participate in data provision and to link and analyze
(herpes), or hands [2]. data for planning and managing care [18].
HSV lies dormant in the nerves until shedding occurs, typically Aim and Objectives
between 2 and 14 days after infection; however, it can take years
before noticeable symptoms appear. Many individuals are Currently, there is no registry for the collection of real-world
unaware that they are infected with HSV as the virus often HSV data. A patient registry whereby people submit information
causes no or mild symptoms. The first shedding episode is themselves, providing real-world data on HSV, could provide
generally associated with severe symptoms (eg, painful sores). more standardized and higher quality data than currently
Patients are typically diagnosed when symptoms are present as available. A patient registry is “an organised system that uses
many methods for the diagnosis of HSV are reliant on viral observational study methods to collect uniform data (clinical
shedding. The techniques for diagnosis in both symptomatic and other) to evaluate specified outcomes for a population
and asymptomatic periods vary in accuracy [3]. The only HSV defined by a particular disease, condition, or exposure, and that
treatment currently available is antiviral therapy (acyclovir or serves one or more predetermined scientific, clinical, or policy
Zovirax), which is prescribed to patients with sores [4]. purposes” [19]. A patient registry could help individuals to
Symptomatic episodes vary in frequency between patients; some understand the triggers and indications of HSV recurrences and
may experience one shedding episode, whereas others can have make changes to their lifestyle to mitigate these symptoms
frequent painful outbreaks triggered by impaired immune where possible. A real-world registry could facilitate research
responses. into the development of vaccines and new, effective treatments,
and examine the impact of HSV on other conditions. The aim
Currently, no Food and Drug Administration–approved of this study was to develop a registry to collect real-world data
therapeutic vaccine is available for HSV [5] as the biology and reported by people who might be infected with HSV. The
biological interactions of HSVs are not comprehensively objectives were to obtain expert opinions on important aspects
understood. It is known that HSV2 can interact biologically of a registry and to provide insights into how specific users
with HIV1; however, the implications for vaccine development might use the registry.
require further elucidation [6]. Previous in vivo studies of HSV
vaccines have been seen to prevent transmission of HSV in pigs, Methods
rodents, and primates, but they are yet to be successful in
humans [7,8]. One therapeutic vaccine, GEN-003, was shown Case Study Overview
to reduce viral shedding and outbreaks of sores in human A case study design was selected to provide a structured means
participants with genital HSV2 infection, but the bioscience to generate in-depth evidence to contribute to the further
company, Genocea, did not pursue this further [9]. development of the proposed registry. We conducted
The lack of available, up-to-date, high-quality, standardized semistructured interviews with experts and analyzed their
data is a key barrier to efficient research, management, and opinions on an HSV registry to establish themes. The results of
treatment of HSV [10]. Clinical registries can be used to collect the thematic analysis were used as the basis for the development
data about individuals with a specific diagnosis or condition on of use cases (a specific user of the registry) that will be applied
a voluntary basis. Typically, this information is contributed by to the development of an RWE registry. A traceability log was
health care providers following consultations with patients [11]. maintained in Microsoft Excel linking the research questions
Clinical registries are used for data collection globally; there to data sources and the study findings.
are more than 60 clinical registries in the United Kingdom [12] This research project brings researchers in contact with people
and the United States [13] and approximately 100 in Sweden who gave their views on the value and development of an HSV
[14] that have contributed to substantial research outputs and registry. The interviewees did not provide information about
quality improvement [15]. themselves and the opinions that they offer were not themselves
Although clinical registries are valuable to research and the subject of research. Therefore, in line with the University
treatment, clinical improvements are primarily long term, with of Oxford guidance, ethical approval was not required.
little direct patient benefit [16]. Other limitations of current
Case Study Framework
registries include the lack of privacy, anonymity, informed
consent, stakeholder feedback, and awareness of existing The case study development followed seven stages, which are
standards and processes when building or maintaining a patient outlined in Table 1.
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Table 1. Case study framework.
Number Stage Outcome
1 Plan Description of case and linking of approach to outcomes.
2 Design Construction of research design and linkage of research questions, data, and criteria for evaluation and synthesis.
3 Prepare Draft, execution, and approval of study protocols.
4 Collect Conduction of semistructured interviews.
5 Analyze Thematic analysis of data.
6 Create Development of use cases for a clinical registry website.
7 Share Presentation of the findings in a report for publication in a peer-reviewed journal (this paper) and sharing with registry
design and production team.
Step 4: Collect
Step 1: Plan
The interviews took place at a location convenient for the
The research question centered on investigating the potential
interviewees and lasted up to an hour. In the interviews, one
of a registry for collecting real-world data contributed by people
researcher asked the questions and followed these up, and
who might be infected with HSV. The focus of the registry was
another researcher took notes (female research assistant Abrar
selected because evidence from the literature suggests that
Alturkistani, MPH, and male analyst Ben Southwood, MA).
although infection with HSV is common, it is not well
The researchers were experienced in conducting qualitative
understood. Furthermore, there is no vaccine or effective
interviews and were knowledgeable about HSV. Although not
treatment for HSV, leading to morbidity for individuals suffering
all interviews were directly transcribed, there was a high level
symptoms of viral shedding. An RWE registry would help
of agreement between the separate sets of notes of the
people with HSV understand their condition and contribute
interviews. The notes mostly comprised direct quotations and
valuable information to the development of vaccines and
paraphrases. The notes were consolidated into a single document
treatment. A case study can be used to inform the development
to code the responses into themes. Transcripts were not sent
of an appropriate real-world registry.
back to the participants.
Step 2: Design
Step 5: Analyze
We designed a case study that involved semistructured
We thematically analyzed the content of the interviews. One
interviews with experts. The findings of these interviews were
researcher built the themes from the first interview and
thematically analyzed. On the basis of these findings, we
reviewed, edited, and refined the themes as the interview process
developed use cases that are reported in this study and will be
went on. A second independent researcher worked on the data
used to design a prototype registry.
following completion of the thematic analysis. We used this
Step 3: Prepare independent coder system to increase the reliability of the coding
We produced a list of 11 experts with different backgrounds, [20]. Later, we compared the two thematic analyses to determine
selected by iterative discussions with a health care expert (HC, consistent, unified themes. The final themes were not centered
Digital Health Lead at Healthcare UK, Department for around any of the questions from the interviews and were instead
International Trade). We chose four experts who were most constructed from the data [21].
relevant to this case study, represented different views, and were Several reviews, discussions, and reconfigurations took place
available for an interview. The interviewees included a male before finalization of a set of themes that justified the source
and female representative (experts 1 and 2) of the Herpes material. After initial coding, the two researchers met on two
Viruses Association, which provides information to people occasions and had several phone calls to discuss differences in
infected with HSV [19], a sexual health consultant with their coding. The themes and subthemes identified were
long-standing interest and published research in HSV repeatedly passed through the data until the smallest coherent
therapeutics (expert 3), and a scientist working on HSV and and consistent set of themes that captured all the insights was
herpes simplex encephalitis (HSE; expert 4). Participants reached. After agreeing on themes, the entire interview text was
provided verbal consent to involvement in the study, note-taking passed through our agreed themes. This allowed us to generate
during conversations, and, in one case, the conversation being a full count of the number of times themes and subthemes
recorded. The list of interview questions was discussed in detail appeared in the interview texts. The findings were not reviewed
in a steering committee meeting and then developed through by the interviewees.
repeated review (HC; Yusuf Ermak, Director KPMG Advisory;
and EM, Research Fellow in Digital Health). The final Step 6: Create
questionnaire had 48 questions and was piloted in the first Having reviewed and finalized the thematic analysis of the
interview (Multimedia Appendix 1). interviews, we developed use cases for the prototype real-world
registry. These were centered around four types of users with
several subtypes. These use cases will inform design work
regarding potential users, their motivations for use, how they
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would access features, and what they would achieve from
interacting with this registry.
Results
Step 7: Share Semistructured Interview Findings
This paper shares the findings of the case study. A high-level summary of the key themes and subthemes
identified in the interviews is provided in Table 2, followed by
a detailed explanation of the themes with quotes. The key themes
were stigma and anonymity, selection bias problems,
understanding treatment gaps and outcomes, lifestyle factors
and causes, individualized versus population-level data, and
severe complications of HSV1/2.
Table 2. Interview themes, count, and subthemes.
Theme Subthemes Count, n
Stigma and anonymity • Root causes 12
• Impact
• Anonymity
• Careful design
Selection bias problems • Being unaware of having an HSVa infection 21
• Available population exaggerates seriousness
• Other selection bias problems
• Ways to ameliorate
Understanding treatment and outcome gaps • Trouble getting treatment 15
• Spatial
• Differences by provider
• Treatment over time
Lifestyle factors and causes • Health and fitness 5
• Sex and dating
Individualized versus population-level data • Genetics of HSV 10
• Broad-based studies
Severe complications of HSV1/2 • HIV 23
• Herpes simplex encephalitis
• Pregnancy and neonatal herpes
• Pain
• Other severe outcomes
• Understanding severe complications
a
HSV: herpes simplex virus.
For stigma-related reasons, anonymity will be an important
Theme 1: Stigma and Anonymity factor to consider when designing the registry as participants
Interviewees mentioned that HSV is stigmatized for different will likely not want their HSV infection status to be revealed.
reasons, including being considered a sexually transmitted It is important not to discourage potential users; therefore, any
infection (STI) and misinterpretation by the public. This was registry must have credible security, options for anonymity, and
thought to start from sex education when people are told that explain data access:
catching a sexually transmitted disease is bad and disgusting.
In addition, HSV1/2 has been stigmatized by the media and by Would have to be extremely discreet to get people to
many jokes about herpes from the early 1980s onward. submit info about themselves. People join our
Furthermore, people think they know that HSV is incurable, association under assumed names, that’s perfectly
but other conditions that stay in the body like herpes are not fine. [Expert 2]
called incurable, including thrush and chicken pox. These The registry needs to be designed with the user and their
findings imply that better education on HSV is required to experience in mind (user centricity), meaning that the data
reduce the psychosocial implications of HSV infection: collection process serves the expectations and needs of users.
In the development frameworks of existing registries, patient
General public and media need to know more—could centricity is limited, thereby reducing utility. Lack of anonymity
lessen psychological impact a great deal. [Expert 1] will result in user concerns about privacy and control over data
when sensitive information is requested. In addition, it was
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thought that terms such as incurable, chronic, attack, victim, practitioners are often less knowledgeable on herpes than sexual
and dramatic red colors should be avoided. health care professionals:
Theme 2: Selection Bias Problems It can be difficult to get hold of because of the messy
The interviewees considered currently available data collection nature of the treatment landscape. Some patients can
methods to be subject to selection bias problems. There are get thru GP and some patients can’t. Some patients
epidemiological herpes studies doing similar things as a registry can repeatedly go to their sexual health clinic, some
but their data are not detailed, longitudinal, and broad enough. can’t. [Expert 1]
It was thought that herpes gets overrepresented by how much A registry that collects more data could work out who is having
it bothers people and, therefore, studies might overestimate the trouble getting treatment. In addition, it could collect follow-up
symptoms by representing the worst cases. A patient registry data as, for example, people who receive acyclovir typically do
could be used to register more people who are affected and not return to their health care professional. Efficacy of treatment
people with minor symptoms who do not visit a health care is another issue, and there have been anecdotal reports on
professional: ineffectiveness or misdiagnosis. A registry should take into
consideration how these current gaps could be improved by
But I think that the beauty of a registry like this would real-world data collection:
be to catch everybody affected, even those with
occasional cold sores that doesn’t visit their GP or At the moment all you have is patient reflection, it
a clinic and isn’t diagnosed with the condition. has to be better than that, maybe a weekly diary.
[Expert 4] otherwise it becomes reflective and three months later
A registry needs to represent a diverse body of people infected they say it was like this...so it has to be real-time.
with HSV, with variable symptom frequency. Interviewees [Expert 3]
expected a registry to attract mostly those experiencing severe A key benefit of a real-world registry would be the ability to
morbidity from HSV infection. A registry must also include collect data on people who are not seen in the health care system.
those with HSV and from diverse sociodemographic Data on these people may reveal new insights into the
backgrounds and age groups. There are an increasing number transmission of HSV and what adds value for people with HSV
of older patients, which means that a purely app-based registry symptoms:
could be biased toward younger generations: Very little data on unmet need, since they don’t
App would bias things to younger people. Actually contact us or anybody else after they’ve been
we do have quite a number of over 50 year olds who diagnosed. “I’ve been sitting in my house for 10 years
suffer from the more severe forms of HSV1—tentative not having relationships—thank God I found you.”
links to Alzheimer’s and dementia. I have a feeling Wide scale research across the general population.
we might lose out to these. True of even websites—but [Expert 1]
maybe websites an easier form. App/website combo
Theme 4: Lifestyle Factors and Causes
might capture with largest swathe. [Expert 4]
The interviewees mentioned that HSV episodes are related to
Future tools to collect HSV data must consider and address all
a low immune response, which can be influenced by lifestyle
the sources of bias. These tools must engage everyone who may
factors; however, the existing evidence is insufficient to detail
have the condition and not just those with frequent recurrences,
the specific lifestyle factors triggering these episodes and
complications, pain, or psychological impacts.
guidance for mitigation:
Selection bias can become more profound during direct data
If people are getting too many outbreaks they may
collection as there would be a subset of users who are more
want to change their lifestyle. Cold sores is like that
likely to complete an extensive questionnaire, for example,
because you get them when you have a cold.
more computer-literate people who have more time, patients
Understanding underlying health/fitness is potentially
with a confirmed diagnosis, and/or those with more frequent
useful. [Expert 2]
and/or severe symptoms keen on being informed on relevant
clinical trials. Lifestyle factors play an important role in the spread and
management of HSV. The use of collecting information
Theme 3: Understanding Treatment and Outcome Gaps regarding interaction between partners is important to consider.
Interviewees indicated gaps in current HSV treatment, A registry could be used to obtain data on how long they have
management, and outcomes. In the United Kingdom, if you get been living with a partner and how many times they had sex:
diagnosed at a sexual health clinic, you get treated free. This Don’t really understand how often patients infect
has resulted in sexual health clinics being shifted to local partners. Have indirect evidence of how quickly
councils and privatized. Given the limited funds at public clinics, people get infected. Think infection diminishes in
people with HSV are often pushed back to their general longer relations. Would be useful to know how long
practitioner after diagnosis and early treatment. This means that in relationship, how often they have sex. [Expert 3]
ongoing treatment and follow-up can be difficult to get as
patients are shunted between services. Furthermore, general In addition, it was noted that dating apps are starting to move
into this area, for example, reminding people about taking STI
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testing or telling other people who do not use a condom to get present with a brain infection we need to give them
screened. acyclovir FAST- and severity correlates with this but
not perfectly. [Expert 4]
Theme 5: Individualized Versus Population-Level Data
The interviewees highlighted the importance of collecting data Furthermore, newborn babies get neonatal herpes usually from
that will be useful for research. It was mentioned that there is the mother during birth. If a man infects a woman toward the
no reliable national data on HSV1 and HSV2 estimates. The end of pregnancy, she may actually have a baby born with severe
focus has been on individualized data, and it is resource neurological damage. It was thought that there is a rise in
intensive to obtain swabs from individual patients. Collecting neonatal herpes, but it was uncertain exactly how much and not
general population–level data would be useful; a registry would enough to be a priority in the UK health care system.
be able to provide individualized and broad RWE. However, it Use Cases
was thought to not be sufficiently informative for researchers.
After completing the thematic analysis, we developed use cases,
It was thought that a registry should also include relevant family
which show potential journeys of users (Table 3). The use cases
history, for example, infectious disease, immunodeficiency,
are drawn from the themes, explaining how people may use the
ethnicity, and anything running in the family:
registry and database. These use cases can broadly be
I think it would give you more real world angle on categorized into members of the public, patients, clinicians, and
how effective therapies are. You would be able to researchers. Several issues were found after an analysis of both
work out more quickly if its effective or not. [Expert the themes and different use cases.
3]
People who have HSV can be categorized into three groups:
The interviewees anticipated that the medical and research those with frequent recurrences, those with mild or rare
community may not be interested in only information that a recurrences, and pregnant women at risk of transmitting the
traditional clinical registry may provide. Links with health care virus vertically during parturition. Those with mild or rare
services data or genetic databases may provide a more useful recurrences might be less motivated to log their data,
long-term source and breadth of data: particularly, if they have concerns around the stigma attached
I think it would be great to know the genomic to HSV. To overcome selection bias, a wide body of patients
consequences of herpes infection, at the moment we needs to be reached. As the proposed HSV registry collects data
use the natural history. [Expert 3] directly from users, considering ways to ensure anonymity is
important. It is additionally important to ask as few questions
Theme 6: Severe Complications of Herpes Simplex Virus as possible to minimize the time and effort required from the
1/2 participant for data collection while ensuring that the data are
The interviewees reported that the majority of HSV cases are comprehensive.
mild and easily manageable, and HSV is usually not especially Lifestyle factors play a major role in the spread and management
harmful to those affected. However, severe HSV cases can be of HSV. People with frequent recurrences of HSV symptoms
debilitating, are not well understood, and require further research are most likely to contribute to an HSV registry that can help
to improve understanding of the pathophysiology behind their them reduce the frequency and severity of symptoms that they
occurrence. In rare cases, HSV can have costly and damaging experience compared with a registry where the data collected
complications (eg, HSE). HIV status will also need to be do not support their personal health. Those that are not infected
considered as HSV infection increases HIV transmission. It was with HSV may be interested in engaging with an HSV registry
thought to be gratifying for the patient to have information to understand the risk factors for acquiring the virus; this is
around why they suffer such a life-threatening disease when so particularly important for immunodeficient individuals such as
many others do not: those with HIV.
Why do some get very strongly affected? Only 5% is Researchers will be interested in using these data to advance
explained by us. Not all due to genetics but we don’t the development of a vaccine and better treatment. To enable a
know any of the other factors. There is no way to population-level view, the registry needs to provide
predict the final outcome of the patient from things interoperability across systems and adhere to the common and
we currently observe—we don’t understand what the widely accepted data. Clinicians will be interested in using this
parameters are that determine the severity of the to improve their clinical knowledge and practice, particularly
infection. We only know that as soon as patients for patients with severe HSV symptoms.
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Table 3. Use cases.
Use case I am a... I want to... So that I can...
Person with HSVa in- Patient with HSV experiencing Keep track of my recurrences and Reduce the number and severity of recurrences
fection frequent recurrences treatments
Patient with HSV experiencing Add information to the database Help the scientific community advance knowledge
mild and/or rare recurrences
Pregnant patient with HSV Learn about neonatal HSV Avoid transmission of HSV to my baby
Researcher HSV1/2 researcher Elucidate interactions between HSV Contribute to novel research to advance the under-
and other conditions or demographic standing of HSV among the scientific and medical
factors community
Herpes simplex encephalitis re- Understand the factors related to severe Prevent HSV infection leading to severe condi-
searcher HSV tions such as encephalitis
Members of the public General public Learn basic facts and risk factors for Reduce risk of infection, understand and adopt
HSV safe practices, and assuage fear and stigma about
HSV
HIV-positive member of public Learn how HIV and HSV1/2 interact Reduce risk transmission of HIV to others
and implications for personal health
Clinicians General practitioner Improve clinical insights about HSV Optimize management of HSV
Sexually transmitted infection Track patients with HSV and related Ensure optimal treatment of patients and mitigate
specialist clinician conditions the risk of severe complications
a
HSV: herpes simplex virus.
generally unaware of having HSV and those with rare or mild
Discussion symptoms may be less interested in enrolling and contributing
Principal Findings data to a registry than people with severe HSV. To address these
limitations, a registry must provide a meaningful return for all
The key themes identified in the interviews were (1) stigma and those contributing data to ensure the breadth of reach and
anonymity of HSV, (2) selection bias, (3) understanding minimize selection biases. A common problem in digital data
treatment and outcome gaps, (4) lifestyle factors and causes, collection is the inverse correlation between engagement and
(5) individualized versus population-level data, and (6) severe number of questions/steps in the user journey. This conflicts
complications of HSV. On the basis of these themes, we with the overarching goal of the registry to obtain a breadth and
developed use cases that show the potential needs and depth of demographic information from the users to maximize
motivations of users. These can be used to explain how people the potential contribution of the registry to research and trial
may use the registry. These use cases can broadly be categorized enrollment. It will be important to ascertain the optimal balance
into members of the public, individuals with HSV, clinicians, between collecting meaningful amounts of data and the effort
and researchers. required from users.
The themes and use cases identified in this study are consistent A potential use of the proposed registry highlighted by the
with the literature. The interviewees reported that HSV can have interviewees was the potential for real-world data to address
a considerable negative psychosocial impact and affect people’s current treatment and knowledge gaps. Only one treatment for
relationships because of the stigma surrounding HSV [22]. Other HSV is currently available—prescribed at physicians’ discretion,
reports corroborate that although people are generally supportive the optimal timing, duration, and effectiveness of which is
of sharing their data for research, they expect their data to be uncertain for both the first onset and subsequent recurrences
anonymized [23]. However, it has been stipulated that people [27]. A registry collecting information on treatment prescription,
may be more comfortable with sharing data if they are asked adherence and efficacy, and timing and severity of recurrence
by a trusted organization (eg, universities, hospitals, or disease could help to address these unknowns. Furthermore, the
foundations) [24]. Addressing privacy concerns is critical in collection of data on the comorbidities of those infected and
the development of an HSV registry, and anonymization is their HSV journey could help to shed light on the interaction
required to provide a secure environment for data sharing [25]. of HSV with other conditions, such as Alzheimer disease and
A second issue raised by the interviewees was different sources general cognitive ability [28,29].
of selection bias. Although the internet is increasingly accessible Furthermore, recurrences of HSV can be influenced by lifestyle
and utilized, it is not ubiquitous. Previous research has shown factors; however, these are not comprehensively understood or
limited adoption in certain sociodemographic groups related to well communicated to infected individuals. The frequency and
language barriers, levels of internet literacy, and geographical severity of symptoms vary among those with HSV and depend
locations [26]. These need to be addressed to reduce selection on a person’s age, gender, immune system, and the route of
bias and maximize the breadth of the data obtained. Another transmission and type of virus [4]. A registry could help people
source of selection bias is that people without symptoms are
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with HSV and researchers to identify the links between life discovery phase, in which we try to better understand the users
events and recurrences and change their lifestyle to mitigate or and use cases, constraints and improvement opportunities; alpha
prevent recurrences. It is additionally not well known why an phase, in which we will develop a prototype of the solution;
HSV infection can lead to more serious, often debilitating beta phase, in which we will build the HSV registry and test
complications, such as encephalitis, in rare cases [30]. A registry and evaluate the registry with a small patient population; and
could be a tool to facilitate research into these areas. the live phase, in which the registry will be available to the
public and continuous iterations and improvement will be made
The interviewees speculated that the medical and research
where necessary.
community may not be interested in engaging with a registry
that provides information comparable with a traditional registry; We have completed the discovery phase where we identified
therefore, links with health care services data and/or genetic the key factors that impact data collection quality, technological
databases may provide a more useful long-term source of data constraints, and potential improvements that can be made for
and give it a more diverse range of use cases. HSV registries. The alpha phase is ongoing, and a prototype of
the registry is being built. The results of the discovery and alpha
Strengths and Limitations of the Study phases will be published subsequently.
The case study design is a strength of this study as it supports
a systematic means of observing the subject of investigation. Further research is needed on testing this registry with different
This research provides a structured means to generate evidence users and implementing and evaluating its feasibility and
to subsequently evaluate such claims by collecting baseline data effectiveness of collecting data to support the development of
for further evaluation. vaccines and treatments as well as addressing numerous
knowledge gaps in this field.
The limitations of this study are that it comprises a single case
study conducted in a UK context, which limits its Conclusions
generalizability to other settings. Only four experts were This case study reports insights from interviews for the
interviewed; however, they reflected different users and development of an appropriate registry for real-world data
provided an in-depth and rigorous insight into the key issues contributed by people with HSV. In existing registries, user
related to an HSV real-world registry. We conducted a thorough centricity is limited, which reduces people’s use of the system.
thematic analysis of the findings of these semistructured The motivations and expectations of users need to be taken into
interviews. Future work can build on our rigorous case study. account when designing the system to overcome the limitations
We built a step-by-step working methodology, according to the of traditional registries. The stigma associated with HSV elicits
principles of case study research, and consolidated all our source critical privacy concerns. People who might be infected with
materials together. The findings were shared with the registry HSV need to have the option to be anonymous, and transparency
design and production team and were presented in this case regarding the use of the data is paramount. A patient registry
study report. could help those affected by HSV to better understand their
condition and reduce or mitigate recurrences. Furthermore, a
Further Research registry could provide researchers and clinicians with a tool to
Work to further develop the user personas identified in this case systematically collect higher quality data for studying HSV
study is underway. Using the agile delivery project management epidemiology and to evaluate the efficacy and cost-effectiveness
framework [31], the project will be delivered in four stages: of treatments and vaccines.
Acknowledgments
This work was funded by the European Institute of Innovation and Technology Health (grant 18654).
Conflicts of Interest
None declared.
Multimedia Appendix 1
Interview questions.
[DOCX File , 17 KB-Multimedia Appendix 1]
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Abbreviations
HSE: herpes simplex encephalitis
HSV: herpes simplex virus
HSV1: herpes simplex virus type 1
HSV2: herpes simplex virus type 2
RWE: real-world evidence
STI: sexually transmitted infection
Edited by G Eysenbach; submitted 06.11.19; peer-reviewed by J Farzi, N Lindström; comments to author 28.11.19; revised version
received 04.12.19; accepted 24.01.20; published 12.03.20
Please cite as:
van Velthoven MH, Lam C, de Cock C, Stenfors T, Chaudhury H, Meinert E
Development of an Innovative Real-World Evidence Registry for the Herpes Simplex Virus: Case Study
JMIR Dermatol 2020;3(1):e16933
URL: http://derma.jmir.org/2020/1/e16933/
doi: 10.2196/16933
PMID:
©Michelle Helena van Velthoven, Ching Lam, Caroline de Cock, Terese Stenfors, Hassan Chaudhury, Edward Meinert. Originally
published in JMIR Dermatology (http://derma.jmir.org), 12.03.2020. This is an open-access article distributed under the terms
of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work, first published in JMIR Dermatology Research, is
properly cited. The complete bibliographic information, a link to the original publication on http://derma.jmir.org, as well as this
copyright and license information must be included.
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